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A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of High-Dose Quetiapine in Patients With Persistent Symptoms of Schizophrenia or Schizoaffective Disorder

J Clin Psychiatry 2012;73(1):13-20
10.4088/JCP.10m06194

Objective: Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d.

Method: A trial was carried out from October 2003–September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of moderate severity (< 30% improvement in total Positive and Negative Syndrome Scale score after ≥ 4 weeks of quetiapine). The 8 week, double-blind study compared continuation of quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary outcomes were adverse events, metabolic side effects, and symptom severity.

Results: Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high-dose group was 3.1% greater (95% CI, −7.8% to 14.0%; P = .76) than in the 800-mg/d group, a value that was within the a priori limit of 16% defined as noninferiority. Both doses of quetiapine were safe and well tolerated. Weight gain was greater in the high-dose group (1.7 kg over 12 weeks; ≥ 7% body weight, n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; ≥ 7% body weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was greater in the high-dose group (95% CI, 0.0–2.5; P = .044). Symptom severity declined, with no significant difference between groups.

Conclusions: The results did not demonstrate any advantage for use of quetiapine outside the approved dose range.

Trial Registration: www.clinicaltrials.gov Identifier: NCT00328978

J Clin Psychiatry 2012; 73(1):13-20​

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